Research progress of MEK1/2 inhibitors and degraders in the treatment of cancer

Optical Control of Small Molecule-Induced Protein Degradation

(2020) Yuta Naro et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

PHOTACs enable optical control of protein degradation

(2020) Martin Reynders et al.   Science Advances

Antibody–PROTAC Conjugates Enable HER2-Dependent Targeted Protein Degradation of BRD4

(2020) Marı́a Maneiro et al.   ACS Chemical Biology

First-in-human phase I study of ARV-110, an androgen receptor (AR) PROTAC degrader in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) following enzalutamide (ENZ) and/or abiraterone (ABI).

(2020) Daniel Peter Petrylak et al.   JOURNAL OF CLINICAL ONCOLOGY

Azo-PROTAC: Novel Light-Controlled Small-Molecule Tool for Protein Knockdown

(2020) Yu-Hui Jin et al.   JOURNAL OF MEDICINAL CHEMISTRY

Enhancing intracellular accumulation and target engagement of PROTACs with reversible covalent chemistry

(2020) Wen-Hao Guo et al.   Nature Communications

Potent and Selective Mitogen-Activated Protein Kinase Kinase 1/2 (MEK1/2) Heterobifunctional Small-molecule Degraders

(2020) Jianping Hu et al.   JOURNAL OF MEDICINAL CHEMISTRY

The PROTAC technology in drug development

(2019) Yutian Zou et al.   CELL BIOCHEMISTRY AND FUNCTION

PROTAC-Mediated Degradation of Bruton’s Tyrosine Kinase Is Inhibited by Covalent Binding

(2019) Christopher P. Tinworth et al.   ACS Chemical Biology

Covalent Ligand Screening Uncovers a RNF4 E3 Ligase Recruiter for Targeted Protein Degradation Applications

(2019) Carl C. Ward et al.   ACS Chemical Biology

Pomalidomide hybrids act as proteolysis targeting chimeras: Synthesis, anticancer activity and B-Raf degradation

(2019) Hong Chen et al.   BIOORGANIC CHEMISTRY

Design and Characterization of SGK3-PROTAC1, an Isoform Specific SGK3 Kinase PROTAC Degrader

(2019) Hannah Tovell et al.   ACS Chemical Biology

Chemoproteomic-Driven Discovery of Covalent PROTACs

(2019) Yiqing Zhou et al.   BIOCHEMISTRY

Reversible Spatiotemporal Control of Induced Protein Degradation by Bistable PhotoPROTACs

(2019) Patrick Pfaff et al.   ACS Central Science

Triazol: a privileged scaffold for proteolysis targeting chimeras

(2019) Li-Wen Xia et al.   Future Medicinal Chemistry

Discovery of a First-in-Class Mitogen-Activated Protein Kinase Kinase 1/2 Degrader

(2019) Jieli Wei et al.   JOURNAL OF MEDICINAL CHEMISTRY

Light-Induced Protein Degradation with Photocaged PROTACs

(2019) Gang Xue et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Targeted protein degradation: expanding the toolbox

(2019) Matthieu Schapira et al.   NATURE REVIEWS DRUG DISCOVERY

Design, Synthesis, and Biological Evaluation of MEK PROTACs

(2019) Stefan Vollmer et al.   JOURNAL OF MEDICINAL CHEMISTRY

Targeting the C481S Ibrutinib-Resistance Mutation in Bruton’s Tyrosine Kinase Using PROTAC-Mediated Degradation

(2018) Alexandru D. Buhimschi et al.   BIOCHEMISTRY

Proteolysis Targeting Chimeras (PROTACs) of Anaplastic Lymphoma Kinase (ALK)

(2018) Chengwei Zhang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

DNA-encoded chemical libraries - achievements and remaining challenges

(2018) Nicholas Favalli et al.   FEBS LETTERS

Molecular mechanisms of drug resistance in ovarian cancer

(2018) Leyla Norouzi-Barough et al.   JOURNAL OF CELLULAR PHYSIOLOGY

Plasticity in binding confers selectivity in ligand-induced protein degradation

(2018) Radosław P. Nowak et al.   Nature Chemical Biology

Encorafenib and Binimetinib: First Global Approvals

(2018) Matt Shirley   DRUGS

Molecular recognition of ternary complexes: a new dimension in the structure-guided design of chemical degraders

(2017) Scott J. Hughes et al.   Essays in Biochemistry

MEK inhibitors under development for treatment of non-small-cell lung cancer

(2017) Chul Kim et al.   EXPERT OPINION ON INVESTIGATIONAL DRUGS

Identification and Characterization of Von Hippel-Lindau-Recruiting Proteolysis Targeting Chimeras (PROTACs) of TANK-Binding Kinase 1

(2017) Andrew P. Crew et al.   JOURNAL OF MEDICINAL CHEMISTRY

Focal necrotizing myopathy with ‘dropped-head syndrome’ induced by cobimetinib in metastatic melanoma

(2017) Marie-Léa Gauci et al.   MELANOMA RESEARCH

Structural basis of PROTAC cooperative recognition for selective protein degradation

(2017) Morgan S Gadd et al.   Nature Chemical Biology

The Ubiquitin Code in the Ubiquitin-Proteasome System and Autophagy

(2017) Yong Tae Kwon et al.   TRENDS IN BIOCHEMICAL SCIENCES

Small-Molecule PROTACS: New Approaches to Protein Degradation

(2016) Momar Toure et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Chemical Space of DNA-Encoded Libraries

(2016) Raphael M. Franzini et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of Bifunctional Oncogenic Target Inhibitors against Allosteric Mitogen-Activated Protein Kinase (MEK1) and Phosphatidylinositol 3-Kinase (PI3K)

(2016) Marcian E. Van Dort et al.   JOURNAL OF MEDICINAL CHEMISTRY

Cobimetinib combined with vemurafenib in advanced BRAFV600-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial

(2016) Paolo A Ascierto et al.   LANCET ONCOLOGY

The Combination of Vemurafenib and Procaspase-3 Activation Is Synergistic in Mutant BRAF Melanomas

(2016) J. Peh et al.   MOLECULAR CANCER THERAPEUTICS

Induced protein degradation: an emerging drug discovery paradigm

(2016) Ashton C. Lai et al.   NATURE REVIEWS DRUG DISCOVERY

Protein Degradation by In-Cell Self-Assembly of Proteolysis Targeting Chimeras

(2016) Honorine Lebraud et al.   ACS Central Science

Selective Small Molecule Induced Degradation of the BET Bromodomain Protein BRD4

(2015) Michael Zengerle et al.   ACS Chemical Biology

Modular PROTAC Design for the Degradation of Oncogenic BCR-ABL

(2015) Ashton C. Lai et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Dual inhibition of allosteric mitogen-activated protein kinase (MEK) and phosphatidylinositol 3-kinase (PI3K) oncogenic targets with a bifunctional inhibitor

(2015) Marcian E. Van Dort et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Tetrahydropyrrolo-diazepenones as inhibitors of ERK2 kinase

(2015) Jeffrey T. Bagdanoff et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Tunable-Combinatorial Mechanisms of Acquired Resistance Limit the Efficacy of BRAF/MEK Cotargeting but Result in Melanoma Drug Addiction

(2015) Gatien Moriceau et al.   CANCER CELL

Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4

(2015) Jing Lu et al.   CHEMISTRY & BIOLOGY

Growth-Inhibitory and Antiangiogenic Activity of the MEK Inhibitor PD0325901 in Malignant Melanoma with or without BRAF Mutations

(2015) Ludovica Ciuffreda et al.   NEOPLASIA

A randomised, double-blind, placebo-controlled trial of trametinib, an oral MEK inhibitor, in combination with gemcitabine for patients with untreated metastatic adenocarcinoma of the pancreas

(2014) Jeffrey R. Infante et al.   EUROPEAN JOURNAL OF CANCER

The clinical development of MEK inhibitors

(2014) Yujie Zhao et al.   Nature Reviews Clinical Oncology

Combined BRAF and MEK Inhibition versus BRAF Inhibition Alone in Melanoma

(2014) Georgina V. Long et al.   NEW ENGLAND JOURNAL OF MEDICINE

NSK-01105 inhibits proliferation and induces apoptosis of prostate cancer cells by blocking the Raf/MEK/ERK and PI3K/Akt/mTOR signal pathways

(2014) Pengfei Yu et al.   TUMOR BIOLOGY

Increased MAPK reactivation in early resistance to dabrafenib/trametinib combination therapy of BRAF-mutant metastatic melanoma

(2014) Georgina V. Long et al.   Nature Communications

Surface plasmon resonance spectroscopy for characterisation of membrane protein–ligand interactions and its potential for drug discovery

(2013) Simon G. Patching   BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES

Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers

(2013) Georgia Hatzivassiliou et al.   NATURE

Posttranslational protein knockdown coupled to receptor tyrosine kinase activation with phosphoPROTACs

(2013) J. Hines et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Discovery of a Novel ERK Inhibitor with Activity in Models of Acquired Resistance to BRAF and MEK Inhibitors

(2013) E. J. Morris et al.   Cancer Discovery

Concurrent MEK2 Mutation and BRAF Amplification Confer Resistance to BRAF and MEK Inhibitors in Melanoma

(2013) Jessie Villanueva et al.   Cell Reports

Discovery of MEK/PI3K dual inhibitor via structure-based virtual screening

(2012) Hwangseo Park et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Enhanced Apoptosis and Tumor Growth Suppression Elicited by Combination of MEK (Selumetinib) and mTOR Kinase Inhibitors (AZD8055)

(2012) S. V. Holt et al.   CANCER RESEARCH

First-in-Human, Phase I Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of RO5126766, a First-in-Class Dual MEK/RAF Inhibitor in Patients with Solid Tumors

(2012) M. Martinez-Garcia et al.   CLINICAL CANCER RESEARCH

Activation and Function of the MAPKs and Their Substrates, the MAPK-Activated Protein Kinases

(2012) M. Cargnello et al.   MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS

ERK Inhibition Overcomes Acquired Resistance to MEK Inhibitors

(2012) G. Hatzivassiliou et al.   MOLECULAR CANCER THERAPEUTICS

Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations

(2012) Keith T. Flaherty et al.   NEW ENGLAND JOURNAL OF MEDICINE

Mechanisms of acquired resistance to ERK1/2 pathway inhibitors

(2012) A S Little et al.   ONCOGENE

Mechanisms of Resistance to RAF Inhibitors in Melanoma

(2011) Andrew E. Aplin et al.   JOURNAL OF INVESTIGATIVE DERMATOLOGY

Activation and Function of the MAPKs and Their Substrates, the MAPK-Activated Protein Kinases

(2011) M. Cargnello et al.   MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS

Strong negative feedback from Erk to Raf confers robustness to MAPK signalling

(2011) R. Fritsche-Guenther et al.   Molecular Systems Biology

Amplification of the Driving Oncogene, KRAS or BRAF, Underpins Acquired Resistance to MEK1/2 Inhibitors in Colorectal Cancer Cells

(2011) A. S. Little et al.   Science Signaling

Discovery of 3-(2-aminoethyl)-5-(3-phenyl-propylidene)-thiazolidine-2,4-dione as a dual inhibitor of the Raf/MEK/ERK and the PI3K/Akt signaling pathways

(2010) Qianbin Li et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Transcriptional Pathway Signatures Predict MEK Addiction and Response to Selumetinib (AZD6244)

(2010) J. R. Dry et al.   CANCER RESEARCH

Phase I Pharmacokinetic and Pharmacodynamic Study of the Oral MAPK/ERK Kinase Inhibitor PD-0325901 in Patients with Advanced Cancers

(2010) P. M. LoRusso et al.   CLINICAL CANCER RESEARCH

BRAF Gene Amplification Can Promote Acquired Resistance to MEK Inhibitors in Cancer Cells Harboring the BRAF V600E Mutation

(2010) R. B. Corcoran et al.   Science Signaling

RDEA119/BAY 869766: A Potent, Selective, Allosteric Inhibitor of MEK1/2 for the Treatment of Cancer

(2009) C. Iverson et al.   CANCER RESEARCH

Impact of Feedback Phosphorylation and Raf Heterodimerization on Normal and Mutant B-Raf Signaling

(2009) D. A. Ritt et al.   MOLECULAR AND CELLULAR BIOLOGY

MEK1 mutations confer resistance to MEK and B-RAF inhibition

(2009) C. M. Emery et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

BRAF V600E Disrupts AZD6244-Induced Abrogation of Negative Feedback Pathways between Extracellular Signal-Regulated Kinase and Raf Proteins

(2008) B. B. Friday et al.   CANCER RESEARCH

Putative allosteric MEK1 and MEK2 inhibitors

(2008) Steve Price   EXPERT OPINION ON THERAPEUTIC PATENTS